Some text in this chapter has been reproduced from Paskins Z, et al. BMJ Open 2020;10:e040634. https://doi.org/10.1136/bmjopen-2020-040634. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) licence, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See https://creativecommons.org/licenses/by/4.0/. The text below includes minor additions and formatting changes to the original text.
Some text in this chapter has been reproduced from Narayanasamy M, Bishop S, Sahota O, Paskins Z, Gittoes N, Langley T. Acceptability and engagement amongst patients on oral and intravenous bisphosphonates for the treatment of osteoporosis in older adults. Age Ageing 2022;51(11):afac255. https://doi.org/10.1093/ageing/afac255. Permission for reuse is in place as per: © The Author(s) 2022. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. The text below includes minor additions and formatting changes to the original text.
Some text, tables and figures in this chapter have been reproduced from Bastounis A, et al. Osteoporos Int 2022;33:1223–3. This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) licence, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See https://creativecommons.org/licenses/by/4.0/. The text, tables and figures below include minor additions and formatting changes to the original text.
Discussion
We have identified, through a systematic review of previous studies on patient and clinician experiences of BP treatment, how patients and HCPs make sense (coherence) of BP by balancing perceptions of need against concerns, how uncertainty prevails about BP perceived effectiveness and a number of individual and service factors that have potential to increase self-efficacy in recommending and adhering to BP. We identified with moderate confidence that BP taking induces fear, but has the potential to engender reassurance, and that both the side effects and special instructions for taking oral BP can be a source of treatment burden. The use of TFA was originally developed to evaluate acceptability of complex interventions. We explored the utility of the TFA from two perspectives, as an explanatory model for both patient and clinician acceptability and engagement. The TFA was useful for understanding and combining patient and clinician viewpoints; however, there was considerable overlap between domains; perceived efficacy, affective attitudes and self-efficacy beliefs are all likely to impinge on sense-making or intervention coherence. The TFA alone does not provide a comprehensive framework for understanding patient acceptability or engagement with medicines. The sense-making aspect of the framework appeared pivotal, and the explanatory value of the framework was enhanced by the incorporation of the NCF to operationalise key engagement-related beliefs.
The systematic review of previous studies was followed by prospective qualitative interviews, which was designed to examine the experiences of alternate BP regimens through the seven TFA domains. This showed that IV BP treatment with ZOL was generally more acceptable to patients than oral BP treatment. Such regimens were perceived to be more straightforward to engage in, although a portion of patients taking oral BP ALN were satisfied with their current treatment. Balancing of the specific TFA domains impacted the extent to which patients with osteoporosis accepted and engaged in their treatment, manifesting as self-efficacy and affective attitude. Crucially, the TFA domains were found to be interconnected, with patients balancing treatment burden, opportunity costs and ethicality issues against treatment coherence and perceived effectiveness. The outcome of this balancing act ultimately determined patients’ attitudes towards, and engagement in, their treatment regimens, thus informing their affective attitudes and self-efficacy. The complexities of using the TFA in the context of examining treatment acceptability found that there were overlaps between TFA domains and that it is not always a comprehensive framework for offering understanding into patient acceptability and engagement with medicines. Other frameworks, such as the NCF, may be helpful in understanding and transforming adherence-related beliefs and behaviours. This framework understands patients’ adherence to be the outcome of a cost–benefit analysis whereby adherence is likely to be higher when the perceived need for treatment is prioritised over the risk of negative consequences such as side effects.
Conducted in parallel to systematic review of previous studies and prospective qualitative interviews, our systematic review and NMA of previous studies of effectiveness found that IV ZOL was the most effective BP compared to ALN, RIS and oral IBN in preventing the occurrence of vertebral fractures and increasing femoral neck BMD. IV ZOL was also found to be comparably effective to RIS and ALN in preventing non-vertebral fractures and hip fractures, respectively. Uptake of IV ZOL was also found to be accompanied by more frequently reported adverse events; however, these events were short-lived. For persistence, results from the NMA from RCTs showed that IV ZOL users may be less likely to drop out from trials at 12 months, although these effects were marginally non-significant. Results from the NMA using data from the observational studies showed that IV ZOL and IBN-IV users were less likely to discontinue their treatment over time, with IV ZOL users being statistically significantly more persistent compared to oral BP users. Data drawn from the vote-counting synthesis were in line with the results of NMAs, where IV ZOL and IBN-IV users were more likely to persist with their treatment, with IV ZOL users being more persistent compared to their IBN-IV counterparts. Due to the paucity of data and the heterogeneity in reporting compliance data, we were unable to perform NMAs, but synthesis based on vote counting found that compliance to IV ZOL was greater within 24 months after the initiation of their treatment. Users of IBN-IV were found to be more compliant compared to IBAN-oral users. Users of ALN were found to be more compliant than RIS users, while mixed evidence were observed in the comparison between ALN and IBN-oral users.
Using data from the systematic review and NMA on effectiveness and NMA on persistence, we updated the previous economic evaluations conducted to inform the NICE appraisal of BP. The previous NICE model made several simplifying assumptions that limited the accuracy of the comparisons between the different BP treatments. For example, long-term persistence with treatment and the incidence of adverse events were assumed to be the same for all oral BP. The key strength of our analysis was that we took a model used previously to inform the NICE appraisal of BP and incorporated our systematic review and NMA on effectiveness and NMA on persistence to better quantify the relative advantages of alternative BP regimens in terms of treatment persistence and adverse effects. It has also included an expected value of perfect information analysis to identify the key areas of decision uncertainty when selecting the optimum BP treatment regimen. Our economic evaluation identified that higher hospital administration costs for IV ZOL meant that there was minimal uncertainty relating to whether IV ZOL was more cost-effective, despite the fact that IV ZOL was predicted to result in fewer fractures than ALN due to having higher treatment persistence and a longer offset period. Whether alternatives to hospital administration, such as IV ZOL delivered in a home care setting, are more cost-effective requires further evaluation.
Our concluding, final prioritisation exercise highlighted topics of importance to stakeholders in the research of BP regimens for the prevention of osteoporotic fracture in adults, refining previously identified priority areas into specific questions. Our top research priority identified was ‘Which people with osteoporosis should be offered IV ZOL first line to optimise medicine effectiveness?’ This could be influenced by a range of different patient factors, which, in turn, would influence treatment selection and effectiveness. Patients are typically not given a choice between oral or IV ZOL. Whilse clinicians may choose to offer IV ZOL on the basis of tolerability and safety issues, more empirical evidence is needed which specifically investigates which patients would benefit most from first-line IV ZOL. Published research recommendations and previous prioritisation exercises largely focus on safety and optimal duration of drug treatment, both of which were included within the top 10 research priorities. However, our top 10 list also highlighted the importance of developing a long-term model of care, providing more support for ongoing medicine optimisation and researching the role of monitoring (bone turnover markers). Overall, of the top 10 identified research priorities in this study, only 3 were derived from guideline recommendations. Particularly novel questions relate to the use of IV ZOL in the community and the best BP regimen for young adults.
Equality, diversity and inclusion
In our qualitative study, our sample population was largely drawn from a sample of participants who had membership with the ROS, with a smaller number recruited through NHS services. The majority of the participants were white. This may have caused the sample to be biased, for example, it may have largely comprised individuals who had the financial means to fund membership and who were possibly taking a more proactive approach to their health by investing in resources. This may restrict its applicability to other patient groups, such as those who are financially disadvantaged and those who are less proactive in their care and treatment.
Future studies may consider recruiting through GP practices. This method may also address some issues related to ethnicity since the majority of our recruited population was white.
In the stakeholder meetings, the stakeholders involved might not be entirely representative of the wider population. The study may not have adequately represented underserved populations, and stakeholders’ ethnicity data were not collected, which may have affected the final questions prioritised. Furthermore, patient and caregiver responses within the workshops may have been influenced by the presence of HCPs.
Future studies may give greater consideration to ethnicity mix in the stakeholder group.
The research team itself was widely representative, with male and female members, members from the BAME community, and experience and expertise across the research team. PPI members were representative of the disease and ongoing treatment modalities. Two junior researchers were supported directly by the senior members with supervised development opportunities.
Conclusions
We have identified the factors that influence how patients and clinicians make sense of BP, describe the experience of BP taking in terms of burden and identified factors that both facilitate and hinder confidence in taking, and prescribing and monitoring BP. Our findings demonstrate the need for a theoretically informed, whole-system approach to enable clinicians and patients to get the best from BP treatment. Patients need comprehensive support that takes account of the perceptions (e.g. treatment necessity beliefs and concerns) and practicalities (e.g. capability and resources) that influence their motivation and ability to start and continue with treatment. IV ZOL treatment was generally more acceptable to patients. IV ZOL was found to be the most effective BP and with greater adherence; however, there was uncertainty relating to whether IV ZOL was more cost-effective due to the high hospital administration costs. The prioritisation exercise highlighted the importance of including stakeholders when setting research priorities and provided a more in-depth understanding of the priorities of stakeholders in BP regimens. While some research priorities, such as supporting people with osteoporosis to make decisions about their treatment are being addressed, the findings illustrate a need to address the issues relating to patient factors influencing treatment selection and effectiveness and how to optimise long-term care.
Further research is needed to explore perspectives of managers, patients receiving IV BP, men receiving BP and the use of BP in the context of multimorbidity. Research is also needed to support people to make decisions influencing treatment selection and effectiveness, and establish how to optimise long-term care, using frameworks for investigating patient acceptability of and engagement in treatment. In addition, research is needed to explore the clinical and cost-effectiveness of IV ZOL delivered in alternate settings, such as the community, compared to ALN treatment.